BRCA gene mutations in cancer

Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes in a 3,552 Japanese whole-genome sequence dataset (3.5KJPNv2)

The paper identifies seven new potentially pathogenic BRCA1/BRCA2 variants in a Japanese population using computational scores and cohort analysis.

Family History Assessment Significantly Enhances Delivery of Precision Medicine in the Genomics Era

This study shows that family history collection improves the detection of pathogenic variants in genomic data, enhancing precision medicine by identifying high-risk individuals.

Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants

The paper evaluates a genotype-first approach for identifying BRCA1/2 variant carriers in a biobank cohort and assesses the impact of risk disclosure.

Transcriptome and interactome analyses identify the TP53 interacting gene RCCD1 as a candidate susceptibility gene at the 15p26.1 breast and ovarian cancer risk locus

The paper identifies RCCD1 as a susceptibility gene for breast and ovarian cancer by fine-mapping a risk locus and showing its expression and interaction patterns are associated with cancer risk.

Inherited rare, deleterious variants in ATM increase lung adenocarcinoma risk

The paper identifies inherited rare, deleterious ATM variants as risk factors for lung adenocarcinoma, showing increased odds ratios in case-control studies and population cohorts.

Precision Breast Cancer Screening with a Polygenic Risk Score

The paper revalidates a polygenic risk score (PRS) model for breast cancer risk prediction and develops a pipeline for individualized screening recommendations using population-specific data.

Prevalence of pathogenic variants in DNA damage response genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer

The paper examines the prevalence of pathogenic variants in DNA damage response genes in early-onset renal cancer patients undergoing genetic testing and finds that DDR gene variants are present in 8.55% of patients.

Population based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high grade serous ovarian cancer

A homozygous hypomorphic BRCA2 variant causes primary ovarian insufficiency without cancer or Fanconi anemia traits.

This study identifies a BRCA2 variant causing primary ovarian insufficiency without cancer or Fanconi anemia, showing residual HR function in patient cells.

Ancestry-Specific Predisposing Germline Variants in Cancer

The paper identifies ancestry-specific germline variants in cancer predisposition genes and their somatic effects across diverse populations.

Mutation prevalence tables for hereditary cancer derived from multi-gene panel testing

The paper develops a tool to estimate mutation prevalence in hereditary cancer genes based on clinical and demographic factors using data from 150,000 multi-gene panel tests.

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

This study identifies 32 new breast cancer susceptibility loci through GWAS, with associations varying by tumor subtype and genetic correlations among subtypes.

Identifying Ashkenazi Jewish BRCA1/2 founder variants in individuals who do not self-report Jewish ancestry

The paper identifies Ashkenazi Jewish BRCA1/2 founder variants in individuals without self-reported Jewish ancestry, showing many lack ancestry reporting but have detectable genetic ancestry and may need BRCA testing.

Prediction of the functional impact of missense variants in BRCA1 and BRCA2 with BRCA-ML

BRCA-ML is a machine learning model trained to predict the functional impact of missense variants in BRCA1 and BRCA2 genes, outperforming existing methods.

Color Data v2: a user-friendly, open-access database with hereditary cancer and hereditary cardiovascular conditions datasets

Color Data v2 provides an updated open-access database with genetic and phenotypic data on hereditary cancer and cardiovascular conditions, including polygenic risk scores and clinical risk models.

Exome Sequencing Reveals a High Prevalence of BRCA1 and BRCA2 Founder Variants in a Diverse Population-Based Biobank

The paper uses exome sequencing and EHR data to find BRCA1/2 pathogenic variants in a diverse biobank population, revealing high prevalence in certain ancestry groups and gaps in knowledge for non-European populations.

How to identify the best index case in families with hereditary breast and ovarian cancer

This study establishes clinical criteria to identify the best index case for genetic testing in HBOC families, showing higher mutation detection rates when using these criteria.

Population-based Relative Risks for Specific Family History Constellations of Breast Cancer

The paper estimates population-based relative risks for breast cancer based on specific family history constellations, finding that multiple affected relatives significantly increase risk.

Risk of differential cancer types over age in families with Li-Fraumeni syndrome: a validation study using multi-center cohorts

The paper estimates cancer-specific penetrance in Li-Fraumeni syndrome using a statistical model and validates it across multiple cohorts, showing age-dependent risk patterns for different cancer types.

Rare, pathogenic germline variants in Fanconi Anemia genes increase risk for squamous lung cancer

The paper identifies rare pathogenic germline variants in Fanconi Anemia genes as risk factors for squamous lung cancer, with BRCA2 showing significant enrichment.

Polygenic prediction of breast cancer: comparison of genetic predictors and implications for screening

This paper compares genetic risk scores for breast cancer, finding that a combined metaGRS2 provides the strongest predictive ability in two cohorts.

A multiplexed homology-directed DNA repair assay reveals the impact of ~1,700 BRCA1 variants on protein function

The paper develops a multiplex HDR assay to assess the functional impact of ~1,700 BRCA1 variants, distinguishing loss-of-function from benign variants.

Accurate functional classification of thousands of BRCA1 variants with saturation genome editing

The paper functionally classifies thousands of BRCA1 variants using saturation genome editing to determine their impact on cancer risk.

Universal Panel Testing of Pancreatic Cancer Cases for Cancer Predisposition

This study tests pancreatic cancer cases for germline variants in HBOC and CRC genes, finding 8.9% and 10.5% of cases carry variants with potential clinical significance.

Custom hereditary breast cancer gene panel selectively amplifies target genes for reliable variant calling

The paper evaluates a custom 13-gene breast cancer panel for variant calling, showing high target capture efficiency and concordance with validated variants.

Inherited BRCA1 epimutation as a novel cause of breast and ovarian cancer

The paper identifies inherited BRCA1 promoter hypermethylation as a novel cause of breast and ovarian cancer in two families without germline BRCA1/2 pathogenic variants.

Nanopore sequencing of full-length BRCA1 mRNA transcripts reveals co-occurrence of known exon skipping events

The paper uses nanopore sequencing to analyze full-length BRCA1 mRNA transcripts, identifying novel isoforms and co-occurring exon skipping events.

Discovery and reporting of clinically-relevant germline variants in advanced cancer patients assessed using whole-exome sequencing

This study reports that 17% of advanced cancer patients have clinically relevant germline variants, with higher rates of cancer-associated variants compared to control cohorts.

Development and validation of a 36-gene sequencing assay for hereditary cancer risk assessment

The paper develops and validates a 36-gene sequencing assay for hereditary cancer risk assessment, showing 100% sensitivity and high specificity across mutation types.

Incorporating calibrated functional assay data into the BRCA1 Ex-UV database

The paper integrates functional assay data with sequence analysis to improve BRCA1 variant classification, adding 146 variants to the Ex-UV database.